系统炎症指标在乙型肝炎肝硬化及乙型肝炎病毒相关肝细胞癌进展中的预测价值

目的探讨系统炎症指标系统炎症指数(system inflammation index,SII)、血小板/淋巴细胞比率(platelet to lymphocyte ratio,PLR)及单核细胞/淋巴细胞比率(monocyte to lymphocyte ratio,MLR)在乙型肝炎肝硬化及乙型肝炎病毒(hepatitis B virus,HBV)相关肝细胞癌(hepatocellular carcinoma,HCC)疾病进展中的预测价值。方法纳入2013年1月1日至2016年12月31日就诊于承德医学院附属医院的110例乙型肝炎患者、86例乙型肝炎肝硬化患者、70例HBV相关HCC患者及54例同期健康体检者为研究对象。检测各组血清白蛋白(albumin,ALB)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBil)、血清C反应蛋白(C reactive protein,CRP)、凝血酶原时间(prothrombin time,PT)、凝血酶原活动度(prothrombin activity,PTA)、中性粒细胞、淋巴细胞、血小板及单核细胞水平。计算SII、PLR及MLR。SII、PLR及MLR与各观察指标的相关性采用Pearson相关性分析。对患者进行随访,根据患者生存状况分为生存组(232例)和病死组(34例)。采用多元Logistic回归分析乙型肝炎肝硬化患者和HBV相关HCC患者病死的独立危险因素。采用受试者工作特征(receiver operator characteristic,ROC)曲线分析SII、PLR及MLR对乙型肝炎肝硬化及HBV相关HCC的诊断价值。结果对照组、乙型肝炎组、乙型肝炎肝硬化组及HBV相关HCC组患者ALB [(45.45±7.23)g/L vs(36.78±7.76)g/L vs(19.46±7.69)g/L vs(12.54±7.39)g/L]、ALT [(34.65±12.36)U/L vs(180.34±119.88)U/L vs(234.68±12.58)U/L vs(486.84±96.38)g/L]、AST [(25.34±13.45)U/L vs(147.42±15.67)U/L vs(263.39±15.84)U/L vs(447.96±16.54)g/L]、TBil [(12.65±1.61)μmol/L vs (69.99±29.80)μmol/L vs(162.63±10.36)μmol/L vs(355.84±23.69)μmol/L]、PT [(11.23±1.62)s vs(19.63±12.11)s vs(30.12±1.62)svs(45.46±12.11)s]、PTA [(80.23±11.09)%vs(62.15±10.43)%vs(50.16±11.54)%vs(40.11±10.37)%]及CRP [(30.23±9.57)mg/L vs(65.78±13.57)mg/L vs(105.69±21.17)mg/L vs(158.39±25.17)mg/L]水平差异有统计学意义(P均<0.001)。其中乙型肝炎组、乙型肝炎肝硬化组及HBV相关HCC组患者ALT、AST、TBil、PT和CRP水平均显著高于对照组,ALB和PTA水平显著低于对照组;乙型肝炎肝硬化组和HBV相关HCC组患者ALT、AST、TBil、PT及CRP水平均显著高于乙型肝炎组,ALB和PTA水平显著低于乙型肝炎组;HBV相关HCC组患者ALT、AST、TBil、PT及CRP水平显著高于乙型肝炎肝硬化组,ALB和PTA水平显著低于乙型肝炎肝硬化组,差异均有统计学意义(P均<0.001)。对照组、乙型肝炎组、乙型肝炎肝硬化组及HBV相关HCC组SII(365.41±42.36 vs 486.65±119.88 vs 541.63±72.58 vs 684.21±96.38)、PLR(93.21±13.45 vs 129.63±45.67 vs 168.63±55.84 vs 236.65±66.54)及MLR(0.16±0.03 vs 0.22±0.03 vs 0.28±0.05 vs 0.34±0.05)差异均有统计学意义(F值分别为65.654、54.541、23.654,P均<0.001),其中乙型肝炎组、乙型肝炎肝硬化组及HBV相关HCC组显著高于对照组(P <0.001),乙型肝炎肝硬化组和HBV相关HCC组显著高于乙型肝炎组;HBV相关HCC组显著高于乙型肝炎肝硬化组,差异均有统计学意义(P均<0.001)。SII、PLR、MLR与AST、ALT、TBil、PT和CRP呈正相关(r>0.7,P<0.001),与ALB和PTA呈负相关(r <-0.7,P <0.001)。病死组SII(601.365±178.65 vs 486.32±119.36)、PLR(259.63±55.47 vs 156.36±66.63)及MLR(0.29±0.10 vs 0.24±0.05)水平显著高于生存组(P <0.001)。多元Logistic回归分析表明,SII≥486.32、PLR≥156.36、MLR≥0.24是乙型肝炎肝硬化患者和HBV相关HCC患者病死的独立危险因素(OR=2.36、2.48、3.16,P <0.05)。SII、PLR、MLR诊断乙型肝炎肝硬化及HBV相关HCC的ROC曲线下的面积(area under curve,AUC)分别为0.732(95%CI:0.699~0.793)、0.728(95%CI:0.658~0.768)和0.729(95%CI:0.653~0.771),差异无统计学意义(z=1.365,P=0.653)。结论高水平SII、PLR和MLR与乙型肝炎肝硬化和HBV相关HCC的进展密切相关,是患者病死的独立危险因素。SII、PLR、MLR对乙型肝炎肝硬化和HBV相关HCC具有一定诊断价值,可在临床中推广应用。

Predictive value of systemic inflammatory indexes on progression of hepatitis B-related liver cirrhosis and hepatitis B virus-related hepatocellular carcinoma

Objective To investigate the predictive value of systemic inflammatory indexes[system inflammation index(SII),platelet to lymphocyte ratio(PLR)and monocyte/lymphocyte ratio(MLR)]on progression of hepatitis B-related liver cirrhosis and hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods Total of 110 patients with hepatitis B,86 patients with hepatitis B-related liver cirrhosis,70 patients with HBV-related HCC and 54 healthy controls in the Affiliated Hospital of Chengde Medical College from January 1 st,2013 to December 31 st,2016 were selected.Serum albumin(ALB),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBil),C reactive protein(CRP),prothrombin time(PT),prothrombin activity(PTA),neutrophils,lymphocytes,platelets and monocytes were detected.SII,PLR and MLR were calculated.The correlation of SII,PLR and MLR with the above indexes were analyzed by Pearson correlation method.The patients were divided into survival group(232 cases)and death group(34 cases)according to the follow-up results.Independent risk factors for death of patients with hepatitis B-related liver cirrhosis and HBV-related HCC were analyzed by multiple Logistic regression analysis.Diagnostic value of SII,PLR and MLR on hepatitis B-related liver cirrhosis and HBV-related HCC were analyzed by receiver operator characteristic(ROC)curve.Results ALB[(45.45±7.23)g/L vs(36.78±7.70)g/L vs(19.46±7.69)g/L vs(12.54±7.39)g/L],ALT[(34.65±12.36)U/L vs(180.34±119.88)U/L vs(234.68±12.58)U/L vs(486.84±96.38)g/L],AST[(25.34±13.45)U/L vs(147.42±15.67)U/L vs(263.39±15.84)U/L vs(447.96±16.54)g/L],TBil[(12.65±1.61)μmol/L vs(69.99±29.80)μmol/L vs(162.63±10.36)μmol/L vs(355.84±23.69)μmol/L],PT[(11.23±1.62)s vs(19.63±12.11)s vs(30.12±1.62)s vs(45.46±12.11)s],PTA[(80.23±11.09)%vs(62.15±10.43)%vs(50.16±11.54)%vs(40.11±10.37)%]and CRP[(30.23±9.57)mg/L vs(65.78±13.57)mg/L vs(105.69±21.17)mg/L vs(158.39±25.17)mg/L]of patients of control group,hepatitis B group,hepatitis B-related liver cirrhosis group and HBV-related HCC group were statistically significant(P<0.001).Levels of ALT,AST,TBil,PT and CRP of patients in hepatitis B group,hepatitis B-related liver cirrhosis group and HBV-related HCC group were significantly higher than those of control group,levels of ALB and PTA were significantly lower than those of control group(all P<0.001).Levels of ALT,AST,TBil,PT and CRP of patients in hepatitis B-related liver cirrhosis group and HBV-related HCC group were significantly higher and levels of ALB and PTA were significantly lower than those of hepatitis B group(P<0.001).Levels of ALT,AST,TBil,PT and CRP of patients in HBV-related HCC group were significantly higher and levels of ALB and PTA were significantly lower than those of hepatitis B-related liver cirrhosis group(P<0.05).SII(365.41±42.36 vs 486.65±119.88 vs 541.63±72.58 vs 684.21±96.38),PLR(93.21±13.45 vs 129.63±45.67 vs 168.63±55.84 vs 236.65±66.54)and MLR(0.16±0.03 vs 0.22±0.03 vs 0.28±0.05 vs 0.34±0.05)of patients in control group,hepatitis B group,hepatitis B-related liver cirrhosis group and HBV-related HCC group were statistically significant(P<0.001).The above indexes of patients in hepatitis B group,hepatitis B-related liver cirrhosis group and HBV-related HCC group were significantly higher than those of control group,which were significantly higher of hepatitis B-related liver cirrhosis group and HBV-related HCC group than those of hepatitis B group,and those of HBV-related HCC group were significantly higher than those of hepatitis B-related liver cirrhosis group(all P<0.001).SII,PLR and MLR were positively correlated with AST,ALT,TBil,PT and CRP,respectively(r>0.7,P<0.001),and were negatively correlated with ALB and PTA,respectively(r<-0.7,P<0.001).SII(486.32±119.36 vs 601.365±178.65),PLR(156.36±66.63 vs 259.63±55.47),MLR(0.24±0.05 vs 0.29±0.10)of patients in death group were significantly higher than those in survival group(all P<0.05).Multiple Logistic regression analysis showed that SII≥486.32,PLR≥156.36 and MLR≥0.24 were independent risk factors for the death of patients with hepatitis B-related liver cirrhosis and patients with HBV-related HCC(OR=2.36,2.48,3.16,P<0.05).The area under curve(AUC)of SII,PLR,MLR for the diagnosis of hepatitis B-related liver cirrhosis and HBV-related HCC were 0.732(95%CI:0.699~0.793),0.728(95%CI:0.658~0.708)and 0.729(95%CI:0.653~0.771),respectively,while the differences were not statistically significant(z=1.365,P=0.653).Conclusions High levels of SII,PLR and MLR are closely related to the progression of hepatitis B-related liver cirrhosis and HBV-related HCC and are risk factors for death prognosis outcomes of patients with hepatitis B-related liver cirrhosis and HBV-related HCC.SII,PLR and MLR have some diagnostic values on hepatitis B-related liver cirrhosis and HBV-related HCC,which is worthy of clinical application.